Window of Opportunity Study of Preoperative Immunotherapy With Atezolizumab in Local SCCHN

NCT04939480 | Completed Phase 2 DMC

• 1 other identifier: MO39839
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Targeting the PD-L1 pathway with atezolizumab has demonstrated objective responses across a broad range of malignancies including head and neck squamous cell carcinoma (SCCHN). MO39839 is a window of opportunity study investigating the feasibility, safety and postoperative complication rates of preoperative short time immunotherapy with atezolizumab in patients with local SCCHN. In the scope of MO39839 a comprehensive translational research program will be conducted to assess the potential effect of atezolizumab on dynamics in tumor immunity, and to identify and validate potential predictive and prognostic biomarkers.

Conditions

Squamous Cell Carcinoma of Head and Neck

Outcome Measures

Primary Outcomes (2)

• Effect of atezolizumab on tumor-infiltrating immune cells in resectable SCCHN

  Percentage of patients with at least 2-fold increase of GzmB+/CD8+ T cells by immunohistochemistry (IHC) after 1 administration of atezolizumab between pre-treatment biopsy specimens and post-treatment resection specimens

  4 weeks

• Feasibility of preoperative short time immunotherapy

  Number of patients with completion of pre-operative immunotherapy and resection of SCCHN

  3 weeks

Secondary Outcomes (7)

• Safety of preoperative short time immunotherapy

  58 days

• Assessment of postoperative complication rates

  30 days

• To assess dynamics in tumor immunity

  21 days

• Characterization of changes in frequency of circulating immune cells

  58 days

• Resectability after immunotherapy

  4 weeks

Study Arms (1)

Atezolizumab

EXPERIMENTAL

Pre-operative administration of atezolizumab 1200 mg followed by definitive resection of the tumor, followed by standard of care radiotherapy or radio-chemotherapy.

Drug: Atezolizumab

Interventions

Atezolizumab DRUG

Atezolizumab 1200 mg intravenous solution

Atezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol. Written informed consent has to be obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. If laboratory or imaging procedures were performed for alternate reasons prior to signing consent, these can be used for screening purposes with consent of the patient. However, all screening examinations and laboratory results must have been obtained within 14 days before first study drug administration (initial tumor imaging: within 28 days before first study drug administration).
• Only patients for whom sufficient tumor material to be judged by the local investigator and which is of adequate quality can be included into the trial. Please refer to section 6.5 for further details on quantity and quality of tumor samples.
• Histologically or cytologically proven SCCHN (cT1-4a, cN0-3, cM0) that is amenable to surgical resection with curative intent based on the decision of the local multidisciplinary tumor board.
• Patients with relapse after primary radio(chemo)-therapy are allowed if a salvage surgery is possible (maximum 20%). Patients should have recovered from the effects of radiation: AE/sequelae should resolves to ≤ grade 2 (no minimum recovery period required).
• Male or female, 18 years of age or older on day of signing informed consent
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
• Life expectancy \>12 weeks
• Adequate hematologic and end-organ function, defined by laboratory test results, obtained within 14 days prior to initiation of study treatment
• Women of childbearing potential: Should have a negative urine or serum pregnancy test within 14 days prior to receiving the first dose of study medication. Agreement to remain abstinent (refrain from heterosexual intercourse) or use a non-hormonal contraceptive method with a failure rate of \< 1% per year during the treatment period and for at least 5 months after last study drug administration

You may not qualify if:

• Evidence of metastatic disease (M1)
• cT4b Stage
• Prior treatment with immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Treatment with investigational therapy within 28 days prior to initiation of study treatment
• Any anti-cancer therapy, including chemotherapy or hormonal therapy, within 4 weeks prior to initiation of study treatment
• Bilateral pleural effusion
• Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to Day 1, Cycle 1. Note: The use of inhaled corticosteroids, physiologic replacement doses of glucocorticoids (i.e. for adrenal insufficiency) and mineralocorticoids (e.g. fludrocortisone) is allowed
• Treatment with a live-attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during the course of the study, and for 5 months after the last dose of atezolizumab
• Treatment with systemic immuno-stimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL-2\]) within 4 weeks or five half-lives of the drug (whichever is longer) prior to initiation of study treatment
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins; known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or to any component of the atezolizumab formulation
• Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the course of the study
• Uncontrolled hypercalcemia (\> 1.5 mmol/L ionized calcium or Ca \> 12 mg/dL or corrected serum calcium \> ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
• Uncontrolled tumor-related pain. Patients requiring narcotic pain medication must be on a stable regimen at study entry
• Pregnant and lactating women
• Acute toxicities from previous therapy that have not resolved to Grade ≤ 1, except for alopecia

Sponsors & Collaborators

• University Hospital, Essen: lead

Study Sites (1)

University Hospital Essen

Essen, 45147, Germany

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Study Officials

• Stefan Kasper-Virchow, Prof. Dr.

  University Hospital, Essen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2021
• First Posted: June 25, 2021
• Study Start: October 6, 2021
• Primary Completion: March 14, 2024
• Study Completion: March 14, 2024
• Last Updated: April 25, 2024

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)